Oral Pathology Department, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2492/503, Porto Alegre, Rio Grande Do Sul, CEP 90035-003, Brazil.
School of Dentistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Med Oncol. 2018 Oct 30;35(12):161. doi: 10.1007/s12032-018-1214-4.
Metabolic alterations in the tumor microenvironment have a complex effect on cancer progression. Extracellular acidity is a consequence of metabolic switch in cancer and results in cell phenotypes with higher resistance to chemotherapeutics. However, mechanisms underlying the relationship between the extracellular acidity and chemoresistance are not clearly understood. This systematic review was carried out by searching the databases PubMed and EMBASE using the keywords "cancer" and "acidosis" or "acidic" and "chemoresistance" or "drug resistance." In vitro and in vivo studies that evaluated the effects of acidification of the tumor microenvironment on chemotherapeutic treatments were included. Literature reviews, letters to the editor, and articles that were not published in English were excluded. The search resulted in a total of 352 articles. After discarding 75 duplicate references, 277 articles were analyzed by sequentially reading through their titles, abstracts, and finally full-text. A total of 14 articles was selected. Acidification of the tumor microenvironment can trigger resistance through different mechanisms, such as increase in drug efflux transporters, inhibition of proton pumps, induction of the unfolded protein response (UPR), and cellular autophagy.
肿瘤微环境中的代谢改变对癌症的进展有复杂的影响。细胞外酸度是癌症代谢转换的结果，导致对化疗药物具有更高抗性的细胞表型。然而，细胞外酸度与化疗耐药性之间的关系的机制尚不清楚。本系统评价通过在数据库 PubMed 和 EMBASE 中使用关键词“癌症”和“酸中毒”或“酸性”和“化疗耐药性”或“药物耐药性”进行搜索来完成。纳入了评估肿瘤微环境酸化对化疗治疗影响的体外和体内研究。排除了文献综述、给编辑的信以及未以英文发表的文章。搜索共产生了 352 篇文章。在排除 75 篇重复参考文献后，通过依次阅读标题、摘要和全文，对 277 篇文章进行了分析。最终选择了 14 篇文章。肿瘤微环境的酸化可以通过不同的机制引发耐药性，例如增加药物外排转运蛋白、抑制质子泵、诱导未折叠蛋白反应（UPR）和细胞自噬。
